title: Proteomic profiling identified multiple short-lived members of the central proteome as the direct targets of the addicted oncogenes in cancer cells.
abstract: "Oncogene addiction" is an unexplained phenomenon in the area of cancer targeted therapy. In this study, we have tested a hypothesis that rapid apoptotic response of cancer cells following acute inhibition of the addicted oncogenes is because of loss of multiple short-lived proteins whose activity normally maintain cell survival by blocking caspase activation directly or indirectly. It was shown that rapid apoptotic response or acute apoptosis could be induced in both A431 and MiaPaCa-2 cells, and quick down-regulation of 17 proteins, which were all members of the central proteome of human cells, was found to be associated with the onset of acute apoptosis. Knockdown of PSMD11 could partially promote the occurrence of acute apoptosis in both MiaPaCa-2 and PANC-1 pancreatic cancer cells. These findings indicate that maintaining the stability of central proteome may be a primary mechanism for addicted oncogenes to maintain the survival of cancer cells through various signaling pathways, and quick loss of some of the short-lived members of the central proteome may be the direct reason for the rapid apoptotic response or acute apoptosis following acute inhibition of the addicted oncogenes in cancer cells. These findings we have presented can help us better understand the phenomenon of oncogene-addiction and may have important implications for the targeted therapy of cancer.
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, China;
authors.forename: Tonggang
authors.initials: T
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.forename: Dawei
authors.initials: D
authors.lastname: Xu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Cheng
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009857:Oncogenes / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000235:genetics; D020543:Proteome / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020543:Proteome; C549955:PSMD11 protein, human; D046988:Proteasome Endopeptidase Complex